We introduce a JINS special section inspired by a symposium presented at INS 2020 in Denver. The symposium was entitled Truly Cross-fit: The Association of Exercise and Cognitive Reserve. The collection of papers herein spans diverse methods, a range of developmental and clinical conditions, and a variety of outcomes all reflecting on the association of exercise and cognition-related outcomes. Taken together, the studies in this Special Section direct us to the variety of dimensions to be considered in understanding this association including what mode, intensity, duration, and timing of physical activity and aspects of age, sex, genetics, baseline characteristics, and disease status moderate these findings. We hope this Special Section will not only provide a framing for important future research on exercise and clinical outcomes but also inspiration to pursue them.